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TLR3 Gene(Protein Coding)

Toll Like Receptor 3

GCID:
GC04P186059
GIFtS:
76
Genes Participants
UDN Logo

Aliases for TLR3 Gene

Aliases for TLR3 Gene

  • Toll Like Receptor 3 2 3
  • Toll-Like Receptor 3 2 5
  • CD283 Antigen 4
  • CD283 3
  • IIAE2 3

External Ids for TLR3 Gene

Previous GeneCards Identifiers for TLR3 Gene

  • GC04P188024
  • GC04P187670
  • GC04P187574
  • GC04P187686
  • GC04P187365
  • GC04P187227
  • GC04P186990
  • GC04P182742

Summaries for TLR3 Gene

Entrez Gene Summary for TLR3 Gene

  • The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It may thus play a role in host defense against viruses. Use of alternative polyadenylation sites to generate different length transcripts has been noted for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for TLR3 Gene

TLR3 (Toll Like Receptor 3) is a Protein Coding gene. Diseases associated with TLR3 include Herpes Simplex Encephalitis 2 and Hiv-1. Among its related pathways are TNF Signaling (sino) and p53 Pathway (RnD). GO annotations related to this gene include identical protein binding and transmembrane signaling receptor activity. An important paralog of this gene is TLR6.

UniProtKB/Swiss-Prot for TLR3 Gene

  • Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response.

Tocris Summary for TLR3 Gene

  • Toll-like receptors (TLRs) are single transmembrane cell-surface receptors, which have a key role in the innate immune system. TLRs generally exist as homodimers (heterodimers have been reported) and are found on immune cells; macrophages, B lymphocytes and mast cells.

Gene Wiki entry for TLR3 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TLR3 Gene

Genomics for TLR3 Gene

Products:

  1. Regulatory Element

Regulatory Elements for TLR3 Gene

Enhancers for TLR3 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around TLR3 on UCSC Golden Path with GeneCards custom track

Promoters for TLR3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TLR3 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the TLR3 gene promoter:

Genomic Location for TLR3 Gene

Chromosome:
4
Start:
186,069,152 bp from pter
End:
186,088,069 bp from pter
Size:
18,918 bases
Orientation:
Plus strand

Genomic View for TLR3 Gene

Genes around TLR3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TLR3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TLR3 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for TLR3 Gene

Proteins for TLR3 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for TLR3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15455-TLR3_HUMAN
    Recommended name:
    Toll-like receptor 3
    Protein Accession:
    O15455
    Secondary Accessions:
    • B2RAI7
    • B7Z7K0
    • E6Y0F0
    • E6Y0F1
    • E9PGH4
    • Q4VAL2
    • Q504W0

    Protein attributes for TLR3 Gene

    Size:
    904 amino acids
    Molecular mass:
    103829 Da
    Quaternary structure:
    • Monomer and homodimer; dimerization is triggered by ligand-binding, the signaling unit is composed of one ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the interaction is required for transport from the ER to the endosomes. Interacts with SRC; upon binding of double-stranded RNA. Interacts with TICAM1 (via the TIR domain) in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated form (via TIR domain) interacts with WDFY1 (via WD repeat 2) in response to poly(I:C) (PubMed:25736436).

    Three dimensional structures from OCA and Proteopedia for TLR3 Gene

    Alternative splice isoforms for TLR3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TLR3 Gene

Proteomics data for TLR3 Gene at MOPED

Protein Expression for TLR3 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for TLR3 Gene

  • Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding.
  • TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes.
  • Glycosylation at Asn 52, Asn 57, Asn 70, Asn 124, Asn 196, Asn 247, Asn 252, Asn 265, Asn 275, Asn 291, Asn 398, Asn 413, Asn 507, Asn 636, and Asn 662
  • Modification sites at PhosphoSitePlus

Other Protein References for TLR3 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for TLR3 (TLR3)

No data available for DME Specific Peptides for TLR3 Gene

Domains & Families for TLR3 Gene

Gene Families for TLR3 Gene

HGNC:
IUPHAR :

Protein Domains for TLR3 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for TLR3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O15455

UniProtKB/Swiss-Prot:

TLR3_HUMAN :
  • ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.
  • Belongs to the Toll-like receptor family.
  • Contains 22 LRR (leucine-rich) repeats.
Domain:
  • ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.
  • Contains 1 LRRCT domain.
  • Contains 1 LRRNT domain.
  • Contains 1 TIR domain.
Family:
  • Belongs to the Toll-like receptor family.
Similarity:
  • Contains 22 LRR (leucine-rich) repeats.
genes like me logo Genes that share domains with TLR3: view

Function for TLR3 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for TLR3 Gene

GENATLAS Biochemistry:
Drosophila transmembrane receptor Toll homolog 3,with the major transcripts,predominantly expressed in placenta and pancreas,involved in immune defense
UniProtKB/Swiss-Prot Function:
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response.

Phenotypes for TLR3 Gene

MGI mutant phenotypes for TLR3:
inferred from 3 alleles
GenomeRNAi human phenotypes for TLR3:
genes like me logo Genes that share phenotypes with TLR3: view

Human Phenotype Ontology for TLR3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TLR3 Gene

MGI Knock Outs for TLR3:

Animal Model Products

  • Taconic Biosciences Mouse Models for TLR3

miRNA for TLR3 Gene

miRTarBase miRNAs that target TLR3

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Transcription Factor Targets and HOMER Transcription for TLR3 Gene

Localization for TLR3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TLR3 Gene

Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane. Early endosome.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TLR3 Gene COMPARTMENTS Subcellular localization image for TLR3 gene
Compartment Confidence
endoplasmic reticulum 5
endosome 5
lysosome 5
plasma membrane 5
vacuole 5
golgi apparatus 4
extracellular 3
cytosol 2
nucleus 2
peroxisome 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for TLR3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IDA 25204797
GO:0005769 early endosome IEA --
genes like me logo Genes that share ontologies with TLR3: view

Pathways & Interactions for TLR3 Gene

genes like me logo Genes that share pathways with TLR3: view

Gene Ontology (GO) - Biological Process for TLR3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001774 microglial cell activation IEA --
GO:0001934 positive regulation of protein phosphorylation IEA --
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002730 regulation of dendritic cell cytokine production IEA --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with TLR3: view

No data available for SIGNOR curated interactions for TLR3 Gene

Drugs & Compounds for TLR3 Gene

Products:

  1. Drug

(22) Drugs for TLR3 Gene - From: PharmGKB, ClinicalTrials, DGIdb, IUPHAR, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Imiquimod Approved, Investigational Pharma Agonist TLR-7 agonist,immunomodulator with antiviral and antitumor activity, Toll-like receptor 7 (TLR7) agonist 132
Aspirin Approved Pharma Channel blocker 1059
polyIC Pharma Agonist 0
tyrosine Nutra 612
Measles vaccines Pharma 0

(16) Additional Compounds for TLR3 Gene - From: Tocris and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Pam3CSK4
112208-00-1
Poly(I:C)
24939-03-5
RWJ 21757
121288-39-9

(5) Tocris Compounds for TLR3 Gene

Compound Action Cas Number
Imiquimod Toll-like receptor 7 (TLR7) agonist 99011-02-6
Pam3CSK4 TLR1/2 agonist; induces cytokine production 112208-00-1
Poly(I:C) TLR3 agonist 24939-03-5
Resiquimod Toll-like receptor 7 (TLR7) agonist 144875-48-9
RWJ 21757 Toll-like receptor 7 (TLR7) agonist 121288-39-9
genes like me logo Genes that share compounds with TLR3: view

Transcripts for TLR3 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for TLR3 Gene

(1) REFSEQ mRNAs :
(18) Additional mRNA sequences :
(50) Selected AceView cDNA sequences:
(5) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for TLR3 Gene

Toll-like receptor 3:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for TLR3 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6
SP1: - -
SP2: -
SP3:

Relevant External Links for TLR3 Gene

GeneLoc Exon Structure for
TLR3
ECgene alternative splicing isoforms for
TLR3

Expression for TLR3 Gene

Products:

  1. Primer

mRNA expression in normal human tissues for TLR3 Gene

mRNA expression in normal human tissues for TLR3 Gene
mRNA expression by BioGPS for TLR3 GenemRNA expression by GTEx for TLR3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TLR3 Gene

This gene is overexpressed in Nasal epithelium (65.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for TLR3 Gene



SOURCE GeneReport for Unigene cluster for TLR3 Gene Hs.657724

mRNA Expression by UniProt/SwissProt for TLR3 Gene

O15455-TLR3_HUMAN
Tissue specificity: Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic cells. Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the TLR that is expressed most strongly in the brain, especially in astrocytes, glia, and neurons.
genes like me logo Genes that share expression patterns with TLR3: view

Primer Products

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners for TLR3 Gene

Orthologs for TLR3 Gene

This gene was present in the common ancestor of animals.

Orthologs for TLR3 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
 Mammalia TLR3 35
  • 83.72 (n)
  • 82.39 (a)
TLR3 36
  • 83 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia TLR3 35
  • 86.25 (n)
  • 84.28 (a)
TLR3 36
  • 84 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Tlr3 35
  • 81.31 (n)
  • 79.93 (a)
Tlr3 16
Tlr3 36
  • 79 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia TLR3 35
  • 99.3 (n)
  • 98.89 (a)
TLR3 36
  • 99 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Tlr3 35
  • 80.16 (n)
  • 80.82 (a)
oppossum
(Monodelphis domestica)
 Mammalia TLR3 36
  • 74 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia TLR3 36
  • 58 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves TLR3 35
  • 66.82 (n)
  • 61.8 (a)
TLR3 36
  • 61 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia TLR3 36
  • 57 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia tlr3 35
  • 59.31 (n)
  • 55.86 (a)
zebrafish
(Danio rerio)
 Actinopterygii tlr3 35
  • 52.99 (n)
  • 49.2 (a)
tlr3 36
  • 47 (a)
 OneToOne
fruit fly
(Drosophila melanogaster)
 Insecta CG5195 37
  • 23 (a)
CG9562 37
  • 26 (a)
Tollo 35
  • 42.12 (n)
  • 30.79 (a)
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP012385 35
  • 29.79 (n)
  • 14.85 (a)
worm
(Caenorhabditis elegans)
 Secernentea C56E6.6 37
  • 24 (a)
Species with no ortholog for TLR3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TLR3 Gene

ENSEMBL:
Gene Tree for TLR3 (if available)
TreeFam:
Gene Tree for TLR3 (if available)

Paralogs for TLR3 Gene

Paralogs for TLR3 Gene

(1) SIMAP similar genes for TLR3 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with TLR3: view

Variants for TLR3 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for TLR3 Gene

TLR3_HUMAN-O15455
The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and Asian ancestry, and confers some natural resistance to HIV-1 infection.

Sequence variations from dbSNP and Humsavar for TLR3 Gene

SNP ID Clin Chr 04 pos Sequence Context AA Info Type
rs3775291 - 186,082,920(-) GTTGA(A/C/G)TATGT reference, missense
rs5743318 - 186,083,895(+) ATGTT(A/T)CAGTA reference, missense
rs5743316 - 186,082,537(+) CTACA(A/T)CAACT reference, missense
rs5743317 - 186,082,605(+) TAGAG(G/T)ATAAT reference, missense
VAR_054887 Herpes simplex encephalitis 2 (HSE2)

Structural Variations from Database of Genomic Variants (DGV) for TLR3 Gene

Variant ID Type Subtype PubMed ID
dgv683n27 CNV Gain 19166990
dgv5851n71 CNV Gain 21882294
nsv881424 CNV Gain 21882294
nsv470097 CNV Gain 18288195
esv2677545 CNV Deletion 23128226
dgv5852n71 CNV Gain 21882294

Variation tolerance for TLR3 Gene

Residual Variation Intolerance Score: 41.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.64; 89.13% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TLR3 Gene

Human Gene Mutation Database (HGMD)
TLR3

Disorders for TLR3 Gene

MalaCards: The human disease database

(26) MalaCards diseases for TLR3 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
herpes simplex encephalitis 2
  • herpes simplex encephalitis, susceptibility to, 2
hiv-1
  • aids, slow progression to
herpes simplex encephalitis
  • herpes simplex meningo-encephalitis
encephalitis
herpes simplex
  • herpesvirus hominis disease
- elite association - COSMIC cancer census association via MalaCards
Search TLR3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TLR3_HUMAN
  • Herpes simplex encephalitis 2 (HSE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269 PubMed:17872438}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.

Relevant External Links for TLR3

Genetic Association Database (GAD)
TLR3
Human Genome Epidemiology (HuGE) Navigator
TLR3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TLR3
genes like me logo Genes that share disorders with TLR3: view

No data available for Genatlas for TLR3 Gene

Publications for TLR3 Gene

  1. Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. (PMID: 18753640) Yang Z. … Zhang K. (N. Engl. J. Med. 2008) 3 4 23 48 67
  2. Oxidative stress enhances toll-like receptor 3 response to double-stranded RNA in airway epithelial cells. (PMID: 19597128) Koarai A. … Ichinose M. (Am. J. Respir. Cell Mol. Biol. 2010) 3 23
  3. TLR3 in human eosinophils: functional effects and decreased expression during allergic rhinitis. (PMID: 19752565) MAYnsson A. … Cardell L.O. (Int. Arch. Allergy Immunol. 2010) 3 23
  4. Investigation of the [-/A]8 and C1236T genetic variations within the human Toll-like receptor 3 gene for association with multiple sclerosis. (PMID: 20483009) Szvetko A.L. … Griffiths L.R. (Neurol. Res. 2010) 3 23
  5. The microtubule regulator stathmin is an endogenous protein agonist for TLR3. (PMID: 20483774) Bsibsi M. … van Noort J.M. (J. Immunol. 2010) 3 23

Products for TLR3 Gene

  • Addgene plasmids for TLR3

Sources for TLR3 Gene

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